Sigrid Le Clerc, Laura Lombardi, Azmeraw T. Amare, Klaus Oliver Schubert, Liping Hou, Scott R. Clark, Sergi Papiol, Micah Cearns, Urs Heilbronner, Franziska Degenhardt, Fasil Tekola-Ayele, Yi-Hsiang Hsu, Tatyana Shekhtman, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Bernhard T. Baune, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Stephane Jamain, Peter Falkai, Andreas Josef Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Stefan Herms, Per Hoffmann, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John R. Kelsoe, Sarah Kittel-Schneider, Ewa Ferensztajn-Rochowiak, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Susan G. Leckband, Alfonso Tortorella, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Vincent Millischer, Marina Mitjans, Francis Mark Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus Maria Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Urban Ösby, Andrea Pfennig, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Claudia Pisanu, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Mario Maj, Gustavo Turecki, Eduard Vieta, Julia Veeh, Stephanie H. Witt, Adam Wright, Peter P. Zandi, Philip B. Mitchell, Michael Bauer, Martin Alda, Marcella Rietschel, Francis J. McMahon, Thomas Gerd Schulze, Jean-Louis Spadoni, Wahid Boukouaci, Jean-Romain Richard, Philippe Le Corvoisier, Caroline Barrau, Jean-François Zagury, Marion Leboyer, Ryad Tamouza
- Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
Metadaten| Author: | Sigrid Le Clerc, Laura Lombardi, Azmeraw T. Amare, Klaus Oliver Schubert, Liping Hou, Scott R. Clark, Sergi Papiol, Micah Cearns, Urs Heilbronner, Franziska DegenhardtORCiDGND, Fasil Tekola-Ayele, Yi-Hsiang Hsu, Tatyana Shekhtman, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella ArdauORCiD, Bárbara AriasORCiD, Jean-Michel AubryGND, Lena Backlund, Abesh Kumar Bhattacharjee, Frank BellivierORCiD, Antonio Benabarre, Susanne BengesserORCiDGND, Joanna BiernackaORCiDGND, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven CichonORCiDGND, Cristiana CruceanuORCiD, Piotr M. Czerski, Nina DalknerORCiD, Alexandre Dayer, Bernhard T. BauneORCiDGND, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Stephane Jamain, Peter FalkaiORCiDGND, Andreas Josef ForstnerORCiDGND, Louise Frisen, Mark A. FryeORCiD, Janice M. FullertonORCiD, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-SerbanescuORCiD, Paul Grof, Ryota Hashimoto, Joanna HauserORCiD, Stefan HermsORCiD, Per HoffmannORCiDGND, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John R. KelsoeORCiD, Sarah Kittel-SchneiderORCiDGND, Ewa Ferensztajn-Rochowiak, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael LandénORCiD, Catharina Lavebratt, Susan G. Leckband, Alfonso Tortorella, Mirko ManchiaORCiD, Lina Martinsson, Michael J. McCarthy, Susan McElroyORCiDGND, Francesc Colom, Vincent Millischer, Marina MitjansORCiD, Francis Mark MondimoreORCiDGND, Palmiero MonteleoneORCiD, Caroline M. Nievergelt, Markus Maria NöthenORCiDGND, Tomas Novák, Claire O'DonovanORCiD, Norio Ozaki, Urban Ösby, Andrea PfennigORCiDGND, James B. Potash, Andreas ReifORCiDGND, Eva ReininghausORCiDGND, Guy A. RouleauORCiD, Janusz K. Rybakowski, Martin Schalling, Peter R. SchofieldORCiD, Barbara W. Schweizer, Giovanni SeverinoORCiD, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Claudia Pisanu, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Mario Maj, Gustavo TureckiORCiD, Eduard VietaORCiDGND, Julia Veeh, Stephanie H. WittORCiDGND, Adam Wright, Peter P. Zandi, Philip B. MitchellORCiD, Michael BauerORCiD, Martin AldaORCiD, Marcella RietschelORCiDGND, Francis J. McMahonORCiD, Thomas Gerd SchulzeORCiDGND, Jean-Louis Spadoni, Wahid Boukouaci, Jean-Romain Richard, Philippe Le Corvoisier, Caroline Barrau, Jean-François Zagury, Marion LeboyerORCiDGND, Ryad Tamouza |
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| URN: | urn:nbn:de:hebis:30:3-632514 |
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| DOI: | https://doi.org/10.1038/s41598-021-97140-7 |
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| ISSN: | 2045-2322 |
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| Parent Title (English): | Scientific reports |
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| Publisher: | Macmillan Publishers Limited, part of Springer Nature |
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| Place of publication: | [London] |
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| Document Type: | Article |
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| Language: | English |
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| Date of Publication (online): | 2021/09/08 |
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| Date of first Publication: | 2021/09/08 |
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| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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| Release Date: | 2022/02/16 |
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| Tag: | Genetics; Immunogenetics; Immunology; Psychiatric disorders |
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| Volume: | 11 |
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| Issue: | art. 17823 |
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| Page Number: | 12 |
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| First Page: | 1 |
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| Last Page: | 12 |
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| Note: | This manuscript was written under the framework of Agence Nationale de la Recherche (I-GIVE ANR-13-SAMA-0004-01), INSERM (Institut National de la Santé et de la Recherche Médicale) and Fondation FondaMental. Laura Lombardi benefits from a fellowship n° FDM202006011305 from Fondation de la Recherche Médicale (FRM). Sven Cichon. and Andreas J Forstner received support from the Swiss National Science Foundation / German Research Foundation (SNSF 310030L_182731/1). This work was in part funded by the Deutsche Forschungsgemeinschaft (DFG; grant no RI 908/7-1; grant FOR2107, RI 908/11-1 to Marcella Rietschel, Michael Bauer, and Thomas G Schulze, NO 246/10-1 to MMN) and the Intramural Research Program of the National Institute of Mental Health (ZIA-MH00284311; NCT00001174). The genotyping was in part funded by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med. This work was supported by the NIH grants P50CA89392 from the National Cancer Institute and 5K02DA021237 from the National Institute of Drug Abuse. The Canadian part of the study was supported by a grant #64410 from the Canadian Institutes of Health Research to MAl. Collection and phenotyping of the Australian UNSW sample was funded by an Australian NHMRC Program Grant (No. 1037196).The collection of the Barcelona sample was supported by the Centro de Investigación en Red de Salud Mental (CIBERSAM) IDIBAPS (grant numbers PI080247, PI1200906, PI12/00018), and Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2014SGR1636 and 2014SGR398). Genotyping for part of the Swedish sample was funded by the Stanley Center for Psychiatric Research at the Broad Institute. The Swedish Research Council, the Stockholm County Council, Karolinska Institutet, and the Söderström-Königska Foundation supported this research through grants awarded to Drs Backlund, Frisen, Lavebratt, and Schalling. The collection of the Geneva sample was supported by grants Synapsy–The Synaptic Basis of Mental Diseases 51NF40-158776 and 32003B-125469 from the Swiss National Foundation. The work by the French group was supported by INSERM (Institut National de la Santé et de la Recherche Médicale), AP-HP (Assistance Publique des Hôpitaux de Paris), the Fondation FondaMental (RTRS Santé Mentale), and the labex Bio-PSY (Investissements d’Avenir program managed by the ANR under reference ANR-11-IDEX- 0004-02). The collection of the Romanian sample was supported by a grant from Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (Dr Grigoroiu-Serbanescu).The collection of the Czech sample was supported by the project Nr. LO1611 with a financial support from the MEYS under the NPU I program and by the Czech Science Foundation, grant Nr. 17-07070S. |
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| HeBIS-PPN: | 491748248 |
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| Institutes: | Medizin |
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| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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| Sammlungen: | Universitätspublikationen |
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| Licence (German): |  Creative Commons - Namensnennung 4.0 |
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Creative Commons - Namensnennung 4.0